Li Shi-Fei, Wang Xiu-Yi, Li Gong-Lu, Jiao Ying-Ying, Wang Wen-Hao, Wu Xing-Kang, Zhang Li-Wei
Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, People's Republic of China.
Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, People's Republic of China; Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, People's Republic of China.
Phytochemistry. 2022 Nov;203:113395. doi: 10.1016/j.phytochem.2022.113395. Epub 2022 Aug 24.
Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the "shock and kill" of latent HIV. In this study, two unreported modified daphnane-type diterpenes (chamaedaphnelide A and epi-chamaedaphnelide A) and one unreported tigliane-type diterpene (chamaedaphnelide B), along with four known daphnane-type diterpenes and one known tigliane-type diterpene were obtained from the leaves of Wikstroemia chamaedaphne. Chamaedaphnelide A and epi-chamaedaphnelide A represents the first A ring cleavage daphnane-type backbone. Chamaedaphnelide A, epi-chamaedaphnelide A, chamaedaphnelide B, and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate displayed equally potential to positive drugs prostratin with reversing latent HIV on more than 100-fold compared to unstimulated cells. Furthermore, the activation of STAT1 was involved in the HIV latency-reversing activity of these diterpenes, firstly demonstrating that daphnane- and tigliane-type diterpenes can rapidly activate STAT1 activity. Indeed, these results also supported that activating STAT1 activity is a pathway for reversing latent HIV.
开发高效的HIV潜伏逆转剂是通过“激活并清除”潜伏的HIV来治疗艾滋病的重要方法。在本研究中，从河朔荛花的叶子中获得了两种未报道的修饰瑞香烷型二萜（河朔荛花内酯A和表河朔荛花内酯A）和一种未报道的大戟烷型二萜（河朔荛花内酯B），以及四种已知的瑞香烷型二萜和一种已知的大戟烷型二萜。河朔荛花内酯A和表河朔荛花内酯A代表了首个具有A环裂解的瑞香烷型骨架。河朔荛花内酯A、表河朔荛花内酯A、河朔荛花内酯B和6α,7α-环氧-5β-羟基-12-脱氧佛波醇-13-癸酸酯显示出HIV潜伏逆转活性，尤其是河朔荛花内酯B和6α,7α-环氧-5β-羟基-12-脱氧佛波醇-13-癸酸酯与阳性药物prostratin相比，在逆转潜伏HIV方面具有同等潜力，比未刺激细胞高出100多倍。此外，STAT1的激活参与了这些二萜的HIV潜伏逆转活性，首次证明瑞香烷型和大戟烷型二萜可以快速激活STAT1活性。事实上，这些结果也支持激活STAT1活性是逆转潜伏HIV的一条途径。
